Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have identified and further characterized a Caenorhabditis elegans gene, CEZF, that encodes a protein with substantial homology to the zinc finger and leucine zipper motifs of the human gene products AF10, MLLT6, and BR140. The first part of the zinc finger region of CEZF has strong similarity to the corresponding regions of AF10 (66%) and MLLT6 (64%) at the cDNA level. As this region is structurally different from previously described zinc finger motifs, sequence homology searches were done. Twenty-five other proteins with a similar motif were identified. Because the functional domain of this motif is potentially disrupted in leukemia-associated chromosomal translocations, we propose the name of leukemia-associated protein (LAP) finger. On the basis of these comparisons, the LAP domain consensus sequence is Cys1-Xaa1-2-Cys2-Xaa9-21-Cys3-Xaa2-4 -Cys4-Xaa4-5-His5-Xaa2-Cys6-Xaa12-46 - Cys7-Xaa2-Cys8, where subscripted numbers represent the number of amino acid residues. We review the evidence that this motif binds zinc, is the important DNA-binding domain in this group of regulatory proteins, and may be involved in leukemogenesis.
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PMID:The leukemia-associated-protein (LAP) domain, a cysteine-rich motif, is present in a wide range of proteins, including MLL, AF10, and MLLT6 proteins. 756 8

The genes AF10 and AF17 have been identified as the basis of the t(10;11) and t(11;17) translocations, events that result in their fusion to the MLL/HRX gene in acute myeloid leukaemias. AF10 and AF17 bear significant homology to each other within their putative zinc finger and leucine zipper domains, although they are diverged outside these regions. The BR140 gene encodes a 140 kDa protein of unknown function that contains a putative zinc finger domain, a leucine zipper region, and, in addition, a bromo domain. The zinc finger and leucine zipper domains of BR140 have significant homology to those of AF10 and AF17, suggesting that it belongs to this newly described gene family and, therefore, could be a target for chromosome translocation. To assess the potential involvement of BR140 in chromosome translocations in leukaemia, the chromosomal location of the BR140 gene has been determined by using several independent methods. A combination of Southern analysis, polymerase chain reactions (PCR) on monochromosomal cell hybrids, and fluorescence in situ hybridisation (FISH) has been used to show that the BR140 gene maps to chromosome band 3p25.
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PMID:Gene BR140, which is related to AF10 and AF17, maps to chromosome band 3p25. 894 9